ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.2469G>T (p.Arg823Ser) (rs587780239)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000116142 SCV000186708 uncertain significance Hereditary cancer-predisposing syndrome 2017-04-17 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000116142 SCV000537542 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-04 criteria provided, single submitter clinical testing
Counsyl RCV000662607 SCV000785251 uncertain significance Fanconi anemia, complementation group J; Neoplasm of ovary 2017-06-13 criteria provided, single submitter clinical testing
GeneDx RCV000590497 SCV000150051 uncertain significance not provided 2018-08-27 criteria provided, single submitter clinical testing This variant is denoted BRIP1 c.2469G>T at the cDNA level, p.Arg823Ser (R823S) at the protein level, and results in the change of an Arginine to a Serine (AGG>AGT). This variant has been reported in an individual with pancreatic cancer (Shindo 2017). BRIP1 Arg823Ser was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the helicase domain VI (Cantor 2011). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether BRIP1 Arg823Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Integrated Genetics/Laboratory Corporation of America RCV000590497 SCV000699696 uncertain significance not provided 2016-01-04 criteria provided, single submitter clinical testing
Invitae RCV000123356 SCV000166679 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2018-12-28 criteria provided, single submitter clinical testing This sequence change replaces arginine with serine at codon 823 of the BRIP1 protein (p.Arg823Ser). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and serine. This variant is present in population databases (rs587780239, ExAC 0.006%). This variant has been reported in several individuals affected with breast cancer or pancreatic cancer (PMID: 17033622, 28767289). ClinVar contains an entry for this variant (Variation ID: 128173). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
True Health Diagnostics RCV000116142 SCV000787966 likely benign Hereditary cancer-predisposing syndrome 2017-06-23 no assertion criteria provided clinical testing

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